Effect Of Early Administration Of Intravenous Beta Blockers In Patients With ST-elevation Myocardial Infarction Before Primary Percutaneous Coronary Intervention. The Early-BAMI trial.

Background

The impact of i.v. β-blockers before primary PCI (pPCI) in STEMI patients on infarct size and clinical outcomes is not well established. There is only one randomized controlled trial (METOCARD-CNIC trial), in which early i.v. metoprolol before pPCI was associated with smaller infarctions and higher LVEF. However, that trial was single blinded and had restrictive inclusion criteria (anterior wall STEMI presenting <6 hours after STEMI onset). The Early-BAMI trial is the first double-blinded, placebo-controlled large multicenter study testing the effect of early i.v. β-blockers before pPCI in a less restricted STEMI population.
In the EARLY-BAMI (Effect of Early Beta-blocker Administration before primary PCI in patients with ST-elevation Myocardial Infarction) trial, which was conducted in the Netherlands and Spain, 683 patients (average age 62, 75 percent male) with acute STEMI symptoms of less than 12 hours duration were randomly assigned to receive the beta blocker metoprolol or a placebo before undergoing angioplasty. The primary endpoint was the severity of the heart attack as measured by magnetic resonance imaging (MRI) at 30 days. Secondary endpoints were levels of cardiac enzymes and number of occurrences of ventricular arrhythmia. Safety endpoints were symptoms of an abnormally slow heart rate, symptoms of abnormally low blood pressure and cardiogenic shock (sudden inability of the heart to pump enough blood to meet the body’s needs).

Main results

At 30 days of follow up, the primary endpoint of average heart attack severity measured by MRI was 15.3± 11.0% of left ventricular volume on average in the beta blockers group, compared with 14.9 ± 11.5% in the placebo group (P=0.616).

Peak and area under the creatine kinase (CK) curve did not differ between both groups.

Left ventricular ejection fraction by MRI was 51.0 ± 10.9% in the metoprolol group and 51.6 ± 10.8% in the placebo group, P=0.68.

Ventricular arrhythmias occurred in 3.6% of patients who received beta blockers and in 6.9% of those who received a placebo (P=0.050), a difference that met the threshold for statistical significance but did not result in a clinically significant difference.

Sixteen patients in the beta blockers group experienced symptoms of an abnormally slow heart rate, symptoms of abnormally low blood pressure, or cardiogenic shock, compared with 21 patients in the placebo group, a difference that again was not statistically significant.

Conclusion

In a non-restricted STEMI population, early intravenous metoprolol before pPCI, was not associated with a reduction in infarct size. Metoprolol reduced the incidence of malignant arrhythmias in the acute phase and was not associated with an increase in adverse events.

Editorial comment: ‘Controversy remains with regard to the benefits of pre-reperfusion intravenous beta-blockade in the setting of pPCI for STEMI. It is unlikely that additional trials using infarct size as a surrogate marker of treatment effect will resolve these issues’